An#bodystructure&func#on

Objec&ves

Youshouldbeableto:ü Definean&bodyü Describean&bodystructureü Comparebetweendifferenttypesorclassesofan&bodyandtheirfunc&on

An#bodies=Immunoglobulin

•  Glycoproteinsfoundinserumand&ssuefluidswhichareproducedinresponsetocontactwithimmunogenicforeignmolecules.Theybindspecificallytothean&genthatinducedthereforma&on.

•  Amajorcomponentofhumoralimmunity.

•  FiveClassesIgM,IgG,IgA,IgDandIgE.

•  Allhavethesamebasican#bodystructure.

BASICANTIBODYSTRUCTUREo  Twoiden&callightchainsλorΚ,

220AA(25KDa).

o  Twoiden&calHeavychains,450AA(50KDa).

o  Covalentandnon-covalentforces.o  Twoiden&calan&genbindingsites.

o  Carbohydrate(CHO).o  Eachlightchainboundtoheavychainby

disulfidebond(L-H)andalso(H-H)

o  Hingeregion

C

C

Ag

Ag

N

N

N

N

CHO

CHO

Variable&ConstantRegions

Constant

regions

Variable

regions

ImmunoglobulinDomainStructure

Agbinding

Effectorfunc#on

1.  Domainsa)  VL&CLb)  VH&CH1-CH3(orCH4)

2.  Oligosaccharides3.  Complementarity

DeterminingRegions(CDR) املناطق احملددة التكميلية

CDR1

CDR2

CDR1

CDR2

CDR3 CDR3

AG

LightchainHeavychain

ABasican#bodybindingsite

ImmunoglobulinFragments

1-Fab– Agbinding– Valence=1– SpecificitydeterminedbyVHandVL

Papain

Fc

Fab

2-Fc–  Effectorfunc&ons

3-F(ab’)2Pepsin

Fc Peptides

F(ab’)2

ImmunoglobulinFragments

Ag Binding

ComplementBindingSiteBinding to Fc

Receptors

An#bodyFunc#ons

Classesofimmunoglobulin

Differences:

•  NumberofbasicsubunitswhichformtheAb•  Thepolypep&desequenceintheheavychainconstantregionsaredifferent,givingdifferentfunc&onalcharacteris&cs

Classesofimmunoglobulin.

1.  IgM - Mu (µ) heavy chains

2.  IgG - Gamma (γ) heavy chains

3.  IgA - Alpha (α) heavy chains

4.  IgD - Delta (δ) heavy chains

5.  IgE - Epsilon (ε) heavy chains

Subclassesofimmunoglobulin.

•  IgG Subclasses: IgG1, IgG2, IgG3 and IgG4

•  IgA subclasses: IgA1 and IgA2

•  No subclasses of IgM, IgD, and IgE

ImmunoglobulinLightChainTypes

1.  Kappa (κ) 60% Human 2.  Lambda (λ) 40% •  Kappa 95% Mouse •  Lambda 5%

IgM

•  10%ofnormalserumIg(1.8mg/ml)

•  Pentamercomposedof5basicIgmonomers

•  10an&genbindingsites

•  Heavychainhasfivedomains

C�4

J Chain

PentamericIgM

•  10lightchains•  10heavychains•  10iden&calan&genbindingsites

•  1Jchain

IgM

•  PredominantAbofprimaryimmuneresponse

•  Mostefficientcomplementfixingan&body

•  Halflife10days

•  Notfoundextravascularly•  GoodatOpsonisa&on

•  FoundatBlymphocytecellsurfaceasamembraneboundmonomer.Hereitactsasacellsurfacereceptorinan&genrecogni&on.

IgG

•  IgG:4subclassesγ1-γ4heavychains•  75%ofnormalserumIg(12mg/ml)

•  Basicmonomerstructure

•  4subclassesIgG1,IgG2,IgG3,IgG4,whichare70%,20%,8%and2%ofthenormalserumIgGinhumans

•  InmousetheseareIgG1,IgG2a,IgG2b,IgG3

•  Lifespan:21days

IgG1, IgG2 and IgG4 IgG3

•  Predominant Ab of a secondary immune response

•  Extravascular

•  Fixes complement IgG3 > IgG1 > IgG2 > IgG4

•  Opsonisation

•  Placental transfer IgG1, 3 and 4

IgG

Lymphocyteormonocyte

IgGBindstocellsurfaceFcreceptorsonlymphocytesandmonocytes

An#gen

IgG

Fcreceptor

IgA

•  IgA 2 subclasses α1, α2 heavy chains

•  10-15% of normal serum Ig

•  In human serum mainly monomeric (above 80%)

•  Subclasses IgA1 and IgA2

•  Predominant Ig in secretions eg. saliva and colostrum and in the gut where it is present as a dimer of two Ig monomers one J chain and one secretory component polypeptide.

•  Life span: 6 days

SecretoryIgA

Secretorycomponentproducedbyepithelialcells.Protec#onfromcleavage.

JChain

SpecialisedfortransporttoareasinwhichAbproducingBcellsareabsenteg.gutandviacolostrumtothenewborn

OriginofSecretoryComponentofsIgA

IgD

•  Verylowlevelsinserumatleast1000foldlowerthanIgG(<1%)

•  Basicmonomerstructure.

•  Foundonthesurfaceofcircula&ngBlymphocytesohenco-expressedwithIgM.

•  Lifespan:3days

Tail Piece

Bcell

An#gen

IgDatcellsurface

Igatthecellsurfaceallowsan#genbindingandtriggersBcellac#va#on

IgE

•  Lowestserumconcentra&ons0.0003mg/ml

•  Basicmonomerstructure

•  Heavychainconsistsof5domains

•  BindstotheFcreceptorsofmastcellsandbasophils.Contactwithan&genssubsequentlyleadstothereleaseofpro-inflammatoryagents

•  Halflife:2days

C�4

IgE and mast cell - activation

Y Y

Ag IgE FcεRI

Histamine PGD2 proteases heparin Cytokines

TNF-α, IL-4 etc

Summary:

By the end you will be able to answer these questions

•  What is antibody? •  Draw and describe the structure of Ab? •  Compare between Ab classes?

•  What are the function of Ab?